MicroRNAs (miRNA) play a key role for morphogenesis or various diseases like cancer. Small RNA, has no protein-encoding sequence, has been indentified to interfere with stability or translational ratio of mRNA. MiRNA is one of the small RNA family and has been analyzed about the synthesis, function and target genes. These researches lead exploitation of new nucleic drugs. Many researches have been reported for relationship between miRNA and rheumatoid arthritis (RA)/osteoarthritis (OA). MiR-146a and -155 were mainly reported for RA, miR-140 was mainly reported for OA including cartilage development. This article was summarized various analysis for miRNA with RA and OA.

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  Primary biliary cirrhosis (PBC) is histologically characterized by chronic nonsuppurative destructive cholangitis (CNSDC) associated with destruction of small bile ducts. The pathogenesis of PBC, predominance of female, or the reason why biliary duct is selectively involved, however, remains unknown. Infectious or non-infectious noxious insults such as xenobiotic chemicals may precipitate in the individual having a genetic background of PBC. Activation of innate immune response seems to be a key event in early PBC, leading to the autoimmune injury of small intrahepatic bile duct. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). In PBC, dysregulated biliary innate immunity, namely hyper-responsiveness to PAMPs, is associated with the pathogenesis of cholangiopathy. Moreover, the targeted biliary epithelial cells (BEC) may play an active role in the perpetuation of autoimmunity by attracting immune cells via chemokine secretion. Biliary innate immune responses induce the production of two chemokines, CX3CL1 (fractalkine) and several Th1 shift chemokines, causing the migration of inflammatory cells including NK cells. TLR 4 ligand-stimulated NK cells destroy autologous BECs in the presence of interferon alpha (IFN-α) synthesized by TLR 3 ligand-stimulated monocytes. These findings give new insights in the pathogenesis of this mysterious disease, PBC.

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  IL-17 secreting helper CD4 T cells (Th17 cells) contribute to a variety of autoimmune diseases such as rheumatoid arthritis. IL-17 acts on neutrophils, macrophages, fibroblasts, or osteocalsts to mediate chronic inflammation and destroy the cartilage. Recently, studies of the spontaneous models of arthritis revealed that activation of innate immunity, such as Toll like receptors, C-type lectin receptors, complement, or ATP induce IL-6 or IL-23 production from macrophages or dendritic cells, which triggers the differentiation of Th17 cells and induces autoimmune arthritis. Although the role of Th17 cells in human rheumatoid arthritis is still controversial, activation of innate immunity and induction of Th17 cells should be associated with the induction of arthritis at least in a part of RA patients. These studies will help elucidate the mechanism of arthritis induction and discover the therapeutic method to prevent it.

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  Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that mainly affects young women, a group usually free of atherosclerosis. As treatment for SLE has improved during recent years and long term survival increased, it has become clear that patients with SLE have increased morbidity and mortality from atherosclerotic cardiovascular disease. Several imaging techniques showed increased prevalence of premature atherosclerosis which was most striking in young patients with SLE. Pathogenesis of atherosclerosis is an inflammatory process. Inflammatory cells and mediators play a key role in the pathogenesis of atherosclerosis. Systemic inflammation and immune dysfunction are thought to accelerate atherosclerosis in patients with SLE as well. Several possible reasons for accelerated atherosclerosis in SLE have been suggested. Traditional coronary risk factors, other coronary risk factors including lipoprotein (a), CRP, homocysteine, inflammatory cytokines, increased vascular damage, lupus related factors and medications may affect the development of atherosclerosis in SLE. Atherosclerosis risk assessment, preventive strategy for accelerated atherosclerosis and its treatment would be required in patients with SLE.

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  Antiphospholipid syndrome (APS) is an autoimmune disorder defined by the presence of antiphospholipid antibodies in plasma of patients with vascular thrombosis and/or pregnancy morbidity. APS is considered the major cause of brain infarction in young adults and is a generally accepted cause of recurrent pregnancy loss. Antiphospholipid antibodies are a heterogeneous group of autoantibodies strongly related to the clinical manifestations of APS and with a widely recognized pathogenic role in thrombosis. In this article, recent clinical and pathophysiological advances in APS are discussed.

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  B cells play central roles in pathogenesis of SLE through autoantibody production, autoantigen-presentation, cytokine production and activation of cognate T cells. Recently, a specific subset of B cells, which exerts immunoregulatory properties via IL-10 production was identified, and dysfunction of these B cells might involved in the pathogenesis of SLE. Currently, various therapies targeting B cells, such as B cell-depletive therapy and B cell regulation molecules seems promising, however, their efficacy and safety in the treatment of SLE should be carefully verified in the future. Because the pathogenesis varies in each patients with SLE, the advent of new era in which therapies can be selected based on an individual immune abnormality is waiting.

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  High concordance rate in monozygotic twins and familial clustering of patients with primary biliary cirrhosis (PBC) indicate the involvement of strong genetic factors in the development of PBC. Recent genome-wide association studies (GWASs) and subsequent meta-analyses in European descent have identified HLA and 21 non-HLA susceptibility loci which are involved in IL12/IL12R signaling, TNF/TLR-NFKB signaling and B cell differentiation in the development of PBC. To identify susceptibility loci for PBC in Japanese population, a GWAS and subsequent replication study was performed in a total of 1327 PBC cases and 1120 healthy controls. In addition to the most significant susceptibility region at HLA, two significant (p<5×10⁻⁸) susceptibility loci (TNFSF15 and POU2AF1) were identified. Although these susceptibility loci are different from those identified in European descent (IL12A, IL12RB2, SPIB), these loci are involved in the same signaling pathways, differentiation of T lymphocyte to Th1 cells and differentiation of B lymphocyte to plasma cells. Among 21 non-HLA susceptibility loci for PBC identified in GWASs of European descent, 10 loci (CD80, IKZF3, IL7R, NFKB1, STAT4, TNFAIP2, CXCR5, MAP3K7IP1, rs6974491, DENND1B) showed significant associations in the Japanese population. The comparative analysis of disease-susceptibility genes in multiple ethnicities may provide an important clue for the dissection of disease-pathogenesis.

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  Fever is one of the critical symptoms of patients in pediatrics field. It indicates inflammatory focus somewhere in the body, and the major causes of fever are infectious diseases. Recent progresses of our knowledge about autoinflammatory syndrome promoted the investigation of the mechanism of fever, and suggested that the pro-inflammatory cytokines are the direct causative agents of fever. The basic science revealed that cooperation of IL-6 and IL-1β induces febrile response. Fever of unknown origin (FUO) remains a challenging problem. Rheumatic diseases, rare infectious diseases, and benign tumors and malignancies are diagnoses to be differentiated. FDG-PET is recently proved a valuable tool for the identification of the etiology in patients with FUO. Since the introduction of biological response modifiers into the treatment of patients with pediatric rheumatic diseases has shifted the therapeutic paradigm, a new concept that the blockade of a unique pro-inflammatory cytokine brings cessation of whole inflammatory responses affected tremendously the clinical medicine. A more investigation of inflammation and its pathophisiology will be needed in pediatric rheumatology.

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  A 72-year-old man developed arthritis of the bilateral shoulders and fingers. X-ray examination of the fingers showed periarticular osteoporosis, joint space narrowing, and cystic changes at the bone ends. Because contrast-enhanced MRI revealed synovial membrane proliferation and osteolysis, a diagnosis of rheumatoid arthritis (RA) was made. Treatment for RA with methotrexate (4 mg/week) was initiated in December 2008. In February 2009, adalimumab administration (40 mg/2 weeks) was initiated. The RA markedly improved, and clinical remission was maintained thereafter. However, in April 2010, relatively well-delineated erythematous plaques accompanied by bullae and scales developed on the bilateral palms, toes, limbs, and the inguinal region. A diagnosis of psoriasis-like eruptions was made by skin biopsy, and adalimumab administration was discontinued. After 4 months, the eruptions improved. Psoriasis-like eruptions due to anti-TNF drugs are rarely observed, but adverse effects require caution. This case is reported along with a review of the literature.

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  IPEX (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked) syndrome is a rare immune disorder characterized by endocrinopathy such as insulin-dependent diabetes and hypothyroidism, intractable diarrhea, and recurrent infections. The mutation of the gene encoding a transcription factor, forkhead box P3 (FOXP3), leads to the dysfunction of regulatory T cells, resulting in systemic autoimmunity. IPEX syndrome is inherited in an X-linked recessive pattern. We report the case of a 12-year-old Japanese girl with IPEX syndrome. She developed severe and prolonged diarrhea with significant weight loss at age ten and was diagnosed with Crohn's disease by endoscopic and pathological finding at age twelve. Her diarrhea responded to corticosteroids, but recurred with tapering of corticosteroids. Eventually, infliximab was initiated to control her diarrhea with fair response. Having suffered from insulin-dependent diabetes since age two with hypothyroidism developing one year later, her clinical symptoms were quite reminiscent of IPEX syndrome. Although flow cytometry analysis revealed low expression of Foxp3 in CD4⁺CD25⁺ T cells compared with healthy controls, no genetic mutation was found in the FOXP3 gene. In contrast to previously reported cases of IPEX syndrome without FOXP3 mutations, our patient was distinct in having had no episodes of recurrent infections.

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  We describe 3 siblings who suffered from marked eosinophilia with organ involvement. One sibling, who experienced cervical lymphadenopathy and peripheral neuropathy with eosinophilia (5,834 cells/μL) following bronchial asthma, was diagnosed with Churg-Strauss syndrome (CSS) according to the criteria of the American College of Rheumatology. Another sibling, who suffered from severe asthma with persistent polyarthritis and eosinophilia (2,496 cells/μL), was also diagnosed with CSS according to the criteria of the Japanese Ministry of Health, Labour and Welfare. The remaining sibling, who had eosinophilic pleuritis with peripheral blood eosinophilia (699 cells/μL), did not fulfill the widely used criteria for CSS or hypereosinophilic syndrome (HES) ; however, he fit the newly proposed criteria for HES. Glucocorticoid treatment relieved their symptoms. Although the diagnoses and the criteria used for diagnosis differed between the siblings, all 3 patients showed common features such as eosinophilia with organ involvement that required treatment, indicating the possibility of familial eosinophilia (FE). Furthermore, the clinical features observed differed substantially from those of previously reported FE patients, therefore, these 3 siblings may be affected by a type of FE distinguishable from those previously described.

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